INTRODUCTION: Acute kidney injury (AKI) is associated with increased mortality. AKI-related mortality trends by US urban and rural counties were assessed. METHODS: In the cross-sectional study, based on the Centers for Disease Control and Prevention WONDER (Wide-ranging ONline Data for Epidemiologic Research) Multiple Cause of Death data, age-standardized mortality with AKI as the multiple cause was obtained among adults aged ≥25 years from 2001-2020, by age, sex, race and ethnicity, stratified by urban-rural counties. Joinpoint regressions were used to assess trends from 2001-2019 in AKI-related mortality rate. Pairwise comparison was used to compare mean differences in mortality between urban and rural counties from 2001-2019. RESULTS: From 2001-2020, age-standardized AKI-related mortality was consistently higher in rural than urban counties. AKI-related mortality (per 100,000 population) increased from 18.95 in 2001 to 29.46 in 2020 in urban counties and from 20.10 in 2001 to 38.24 in 2020 in rural counties. In urban counties, AKI-related mortality increased annually by 4.6% during 2001-2009 and decreased annually by 1.8% until 2019 (p<0.001). In rural counties, AKI-related mortality increased annually by 5.0% during 2001-2011 and decreased by 1.2% until 2019 (p<0.01). The overall urban-rural difference in AKI-related mortality was greater after 2009-2011. AKI-related mortality was significantly higher among older adults, men, and non-Hispanic Black adults than their counterparts in both urban and rural counties. Higher mortality was concentrated in rural counties in the Southern United States. CONCLUSIONS: Multidisciplinary efforts are needed to increase AKI awareness and implement strategies to reduce AKI-related mortality in rural and high-risk populations.

Rationale & Objective: The 2021 CKD-EPI removes Black race as a factor in calculating the estimated glomerular filtration rate (eGFR). We assessed its effect on CKD prevalence in the demographically-diverse US Military Health System. Study Design: A retrospective calculation of the eGFR from serum creatinine measured over 2016-2019 using both the 2009 and 2021 CKD-EPI equations. Setting & Population: Multicenter health care network with data from 1,502,607 adults in the complete case analysis and from 1,970,433 adults in an imputed race analysis. Predictors: Serum creatinine, age, sex, and race. Outcome: CKD stages 3-5, defined as the last eGFR persistently < 60 mL/min/1.73m2 for ≥90 days. Analytical Approach: The t test and Kruskal-Wallis test were used for continuous variables and Χ2 for categorical data. Results: The population in the complete case analysis had a median age of 40 years and was 18.8% Black race and 35.4% female. With the 2021 equation, the number of Black adults with CKD stages 3-5 increased by 58.1% from 4,147 to 6,556, a change in the crude prevalence from 1.47% to 2.32%. The number of non-Black adults with CKD stages 3-5 decreased by 30.4% from 27,596 to 19,213, a crude prevalence change from 2.26% to 1.58%. Similar results were seen with race imputation. Cumulatively, among adults with CKD stages 3-5 by at least one equation, 45.8% of Black adults were reclassified to more advanced stages of CKD and 44.0% of non-Black adults were reclassified to less severe stages across eGFR thresholds that could change clinical management. Limitations: Potential underestimation of CKD in individuals with only 1 measurement. Conclusions: Adoption of the 2021 CKD-EPI equation in the Military Health System reclassifies many Black adults into new CKD stages 3-5 or into more advanced CKD stages, with the opposite effect on non-Black adults. This may have an effect on CKD treatment and outcomes in ways that are yet unknown. Plain-Language Summary: Until recently, kidney function level was calculated from equations that adjusted the result if the individual was of Black race. Because this may contribute to racial disparities in kidney disease care, a new equation was developed in 2021 that excludes race as a factor. We assessed the possible effects of this equation using data from adults in the US Military Health System from 2016 to 2019. With the new equation, the number of Black adults classified with kidney disease increased while that of non-Black adults decreased. There were similar trends seen in the more severe levels of kidney disease, which could affect decisions in clinical care. These results emphasize the potential positive and negative outcomes to be monitored with the new equation. © 2024 The Authors

BACKGROUND: The purpose of this study was to examine the association between racial and economic segregation and diabetes mortality among US counties from 2016 to 2020. METHODS: We conducted a cross-sectional ecological study that combined county-level diabetes mortality data from the National Vital Statistics System and sociodemographic information drawn from the 2016-2020 American Community Survey (n=2380 counties in the USA). Racialized economic segregation was measured using the Index Concentration at the Extremes (ICE) for income (ICE(income)), race (ICE(race)) and combined income and race (ICE(combined)). ICE measures were categorised into quintiles, Q1 representing the highest concentration and Q5 the lowest concentration of low-income, non-Hispanic (NH) black and low-income NH black households, respectively. Diabetes was ascertained as the underlying cause of death. County-level covariates included the percentage of people aged ≥65 years, metropolitan designation and population size. Multilevel Poisson regression was used to estimate the adjusted mean mortality rate and adjusted risk ratios (aRR) comparing Q1 and Q5. RESULTS: Adjusted mean diabetes mortality rate was consistently greater in counties with higher concentrations of low-income (ICE(income)) and low-income NH black households (ICE(combined)). Compared with counties with the lowest concentration (Q1), counties with the highest concentration (Q5) of low-income (aRR 1.93; 95% CI 1.79 to 2.09 for ICE(income)), NH black (aRR 1.93; 95% CI 1.79 to 2.09 for ICE(race)) and low-income NH black households (aRR 1.32; 95% CI 1.18 to 1.47 for ICE(combined)) had greater diabetes mortality. CONCLUSION: Racial and economic segregation is associated with diabetes mortality across US counties.

OBJECTIVE: We examined national trends in diabetes-related complications (heart failure [HF], myocardial infarction [MI], stroke, end-stage renal disease [ESRD], nontraumatic lower-extremity amputation [NLEA], and hyperglycemic crisis) among U.S. adults with diagnosed diabetes during 2000-2020 by age-group, race and ethnicity, and sex. We also assessed trends in inequalities among those subgroups. RESEARCH DESIGN AND METHODS: Hospitalization rates for diabetes-related complications among adults (≥18 years) were estimated using the 2000-2020 National (Nationwide) Inpatient Sample. The incidence of diabetes-related ESRD was estimated using the United States Renal Data System. The number of U.S. adults with diagnosed diabetes was estimated from the National Health Interview Survey. Annual percent change (APC) was estimated for assessment of trends. RESULTS: After declines in the early 2000s, hospitalization rates increased for HF (2012-2020 APC 3.9%, P < 0.001), stroke (2009-2020 APC 2.8%, P < 0.001), and NLEA (2009-2020 APC 5.9%, P < 0.001), while ESRD incidence increased (2010-2020 APC 1.0%, P = 0.044). Hyperglycemic crisis increased from 2000 to 2020 (APC 2.2%, P < 0.001). MI hospitalizations declined during 2000-2008 (APC -6.0%, P < 0.001) and were flat thereafter. On average, age inequalities declined for hospitalizations for HF, MI, stroke, and ESRD incidence but increased for hyperglycemic crisis. Sex inequalities increased on average for hospitalizations for stroke and NLEA and for ESRD incidence. Racial and ethnic inequalities declined during 2012-2020 for ESRD incidence but increased for HF, stroke, and hyperglycemic crisis. CONCLUSIONS: There was a continued increase of several complications in the past decade. Age, sex, and racial and ethnic inequalities have worsened for some complications.

BACKGROUND: Mechanisms underlying the pro gression of diabetic kidney disease to ESKD are not fully understood. METHODS: We performed global microRNA (miRNA) analysis on plasma from two cohorts consisting of 375 individuals with type 1 and type 2 diabetes with late diabetic kidney disease, and targeted proteomics analysis on plasma from four cohorts consisting of 746 individuals with late and early diabetic kidney disease. We examined structural lesions in kidney biopsy specimens from the 105 individuals with early diabetic kidney disease. Human umbilical vein endothelial cells were used to assess the effects of miRNA mimics or inhibitors on regulation of candidate proteins. RESULTS: In the late diabetic kidney disease cohorts, we identified 17 circulating miRNAs, represented by four exemplars (miR-1287-5p, miR-197-5p, miR-339-5p, and miR-328-3p), that were strongly associated with 10-year risk of ESKD. These miRNAs targeted proteins in the axon guidance pathway. Circulating levels of six of these proteins-most notably, EFNA4 and EPHA2-were strongly associated with 10-year risk of ESKD in all cohorts. Furthermore, circulating levels of these proteins correlated with severity of structural lesions in kidney biopsy specimens. In contrast, expression levels of genes encoding these proteins had no apparent effects on the lesions. In in vitro experiments, mimics of miR-1287-5p and miR-197-5p and inhibitors of miR-339-5p and miR-328-3p upregulated concentrations of EPHA2 in either cell lysate, supernatant, or both. CONCLUSIONS: This study reveals novel mechanisms involved in progression to ESKD and points to the importance of systemic factors in the development of diabetic kidney disease. Some circulating miRNAs and axon guidance pathway proteins represent potential targets for new therapies to prevent and treat this condition.

BACKGROUND: Simultaneous urine testing for albumin (UAlb) and serum creatinine (SCr), that is, 'dual testing,' is an accepted quality measure in the management of diabetes. As chronic kidney disease (CKD) is defined by both UAlb and SCr testing, this approach could be more widely adopted in kidney care. OBJECTIVE: We assessed time trends and facility-level variation in the performance of outpatient dual testing in the integrated Veterans Health Administration (VHA) system. DESIGN, SUBJECTS AND MAIN MEASURES: This retrospective cohort study included patients with any inpatient or outpatient visit to the VHA system during the period 2009-2018. Dual testing was defined as UAlb and SCr testing in the outpatient setting within a calendar year. We assessed time trends in dual testing by demographics, comorbidities, high-risk (eg, diabetes) specialty care and facilities. A generalised linear mixed-effects model was applied to explore individual and facility-level predictors of receiving dual testing. KEY RESULTS: We analysed data from approximately 6.9 million veterans per year. Dual testing increased, on average, from 17.4% to 21.2%, but varied substantially among VHA centres (0.3%-43.7% in 2018). Dual testing was strongly associated with diabetes (OR 10.4, 95% CI 10.3 to 10.5, p<0.0001) and not associated with VHA centre complexity level. However, among patients with high-risk conditions including diabetes, <50% received dual testing in any given year. As compared with white veterans, black veterans were less likely to be tested after adjusting for other individual and facility characteristics (OR 0.93, 95% CI 0.92 to 0.93, p<0.0001). CONCLUSIONS: Dual testing for CKD in high-risk specialties is increasing but remains low. This appears primarily due to low rates of testing for albuminuria. Promoting dual testing in high-risk patients will help to improve disease management and patient outcomes.

AIMS: Glycoprotein acetyls (GlycA) is a biomarker of systemic inflammation and cardiovascular disease, yet little is known about its role in type 1 diabetes (T1D). We examined the associations among GlycA, central adiposity, insulin resistance, and early kidney injury in youth with T1D. METHODS: Glomerular filtration rate (GFR) and renal plasma flow (RPF) by iohexol and p-aminohippurate clearance, urine albumin-to-creatinine ratio (UACR), central adiposity by DXA, and estimated insulin sensitivity were assessed in fifty youth with T1D (16±3.0 years, 50% female, HbA(1c) 8.7±1.3%, T1D duration 5.7±2.6 years). Concentrations of GlycA were quantified by targeted nuclear magnetic resonance spectroscopy. Correlation and multivariable linear regression analyses were performed. RESULTS: GlycA was higher in girls vs. boys (1.05±0.26 vs. 0.84±0.15 mmol/L, p=0.001) and in participants who were overweight/obese vs. normal weight (1.12±0.23 vs. 0.87±0.20 mmol/L, p=0.0004). GlycA correlated positively with estimated intraglomerular pressure (r=0.52, p=0.001), UACR (r=0.53, p<0.0001) and trunk mass (r=0.45, p=0.001), and inversely with estimated insulin sensitivity (r:-0.36, p=0.01). All relationships remained significant after adjustment for age, sex, and HbA(1c). CONCLUSION: GlycA, a biomarker of inflammation, was higher in girls and those of overweight or obese body habitus in T1D. Additionally, GlycA associated with parameters of early kidney dysfunction, central adiposity, and insulin resistance.

INTRODUCTION: Physical activity (PA) can reduce morbidity and mortality among adults with diabetes. While rural disparities in PA exist among the general population, it is not known how these disparities manifest among adults with diabetes. METHODS: Data from the 2020 and 2022 National Health Interview Survey were analyzed in 2023 to assess prevalence of meeting aerobic and muscle-strengthening recommendations according to the 2018 Physical Activity Guidelines for Americans during leisure time. PA prevalence was computed by diabetes status, type of PA, and urban/rural residence (large central metro, large fringe metro, medium/small metro, and non-metro). Logistic regression models were used to estimate prevalence and prevalence ratios of meeting PA recommendations by urban/rural residence across diabetes status. RESULTS: Among adults with diabetes in non-metro counties, only 23.8% met aerobic, 10.9% met muscle-strengthening, and 6.2% met both PA recommendations. By contrast, among adults with diabetes in large fringe metro counties, 32.1% met aerobic, 19.7% met strengthening, and 12.0% met both guidelines. Multivariable adjusted prevalence of meeting muscle-strengthening recommendations was higher among participants with diabetes in large fringe metro compared to large central metro counties (PR=1.27; 95% CI 1.03-1.56). Among those without diabetes, adjusted prevalence of meeting each recommendation or both was lower in non-metro and small/medium metro compared to large central metro counties. CONCLUSIONS: Adults with diabetes are less likely to meet the PA recommendations than those without, and differences exist according to urban/rural status. Improving PA among rural residents with diabetes may mitigate disparities in diabetes-related mortality.

Although diabetes and cardiovascular disease account for substantial disease prevalence among adults in the United States, their prevalence among racial and ethnic subgroups is inadequately characterized. To fill this gap, CDC described the prevalence of diagnosed cardiometabolic diseases among U.S. adults, by disaggregated racial and ethnic subgroups, among 3,970,904 respondents to the Behavioral Risk Factor Surveillance System during 2013-2021. Prevalence of each disease (diabetes, myocardial infarction, angina or coronary heart disease, and stroke), stratified by race and ethnicity, was based on self-reported diagnosis by a health care professional, adjusting for age, sex, and survey year. Overall, mean respondent age was 47.5 years, and 51.4% of respondents were women. Prevalence of cardiometabolic diseases among disaggregated race and ethnicity subgroups varied considerably. For example, diabetes prevalence within the aggregated non-Hispanic Asian category (11.5%) ranged from 6.3% in the Vietnamese subgroup to 15.2% in the Filipino subgroup. Prevalence of angina or coronary heart disease for the aggregated Hispanic or Latino category (3.8%) ranged from 3.1% in the Cuban subgroup to 6.3% in the Puerto Rican subgroup. Disaggregation of cardiometabolic disease prevalence data by race and ethnicity identified health disparities among subgroups that can be used to better help guide prevention programs and develop culturally relevant interventions.

Estimation of mortality rates and mortality rate ratios (MRR) of diseased and non-diseased individuals is a core metric of disease impact used in chronic disease epidemiology. Estimation of mortality rates is often conducted through retrospective linkage of information from nationwide surveys such as the National Health Interview Survey (NHIS) and death registries. These surveys usually collect information on disease status during only one study visit. This infrequency leads to missing disease information (with right censored survival times) for deceased individuals who were disease-free at study participation, and a possibly biased estimation of the MRR because of possible undetected disease onset after study participation. This occurrence is called "misclassification of disease status at death (MicDaD)" and it is a potentially common source of bias in epidemiologic studies. In this study, we conducted a simulation analysis with a high and a low incidence setting to assess the extent of MicDaD-bias in the estimated mortality. For the simulated populations, MRR for diseased and non-diseased individuals with and without MicDaD were calculated and compared. Magnitude of MicDaD-bias depends on and is driven by the incidence of the chronic disease under consideration; our analysis revealed a noticeable shift towards underestimation for high incidences when MicDaD is present. Impact of MicDaD was smaller for lower incidence (but associated with greater uncertainty in the estimation of MRR in general). Further research can consider the amount of missing information and potential influencers such as duration and risk factors of the disease.

Fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) are both used to diagnose diabetes, but these measurements can identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening, had elevated FPG, HbA1c or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardized proportion of diabetes that was previously undiagnosed and detected in survey screening ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the age-standardized proportion who had elevated levels of both FPG and HbA1c was 29-39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c was more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global shortfall in diabetes diagnosis and surveillance.

OBJECTIVE: Race and ethnicity data disaggregated into detailed subgroups may reveal pronounced heterogeneity in diabetes risk factors. We therefore used disaggregated data to examine the prevalence of type 2 diabetes risk factors related to lifestyle behaviors and barriers to preventive care among adults in the U.S. RESEARCH DESIGN AND METHODS: We conducted a pooled cross-sectional study of 3,437,640 adults aged ≥18 years in the U.S. without diagnosed diabetes from the Behavioral Risk Factor Surveillance System (2013-2021). For self-reported race and ethnicity, the following categories were included: Hispanic (Cuban, Mexican, Puerto Rican, Other Hispanic), non-Hispanic (NH) American Indian/Alaska Native, NH Asian (Chinese, Filipino, Indian, Japanese, Korean, Vietnamese, Other Asian), NH Black, NH Pacific Islander (Guamanian/Chamorro, Native Hawaiian, Samoan, Other Pacific Islander), NH White, NH Multiracial, NH Other. Risk factors included current smoking, hypertension, overweight or obesity, physical inactivity, being uninsured, not having a primary care doctor, health care cost concerns, and no physical exam in the past 12 months. RESULTS: Prevalence of hypertension, lifestyle factors, and barriers to preventive care showed substantial heterogeneity among both aggregated, self-identified racial and ethnic groups and disaggregated subgroups. For example, the prevalence of overweight or obesity ranged from 50.8% (95% CI 49.1-52.5) among Chinese adults to 79.8% (73.5-84.9) among Samoan adults. Prevalence of being uninsured among Hispanic subgroups ranged from 11.4% (10.9-11.9) among Puerto Rican adults to 33.0% (32.5-33.5) among Mexican adults. CONCLUSIONS: These findings underscore the importance of using disaggregated race and ethnicity data to accurately characterize disparities in type 2 diabetes risk factors and access to care.

Aim: This study assessed changes in testing for blood glucose in the United States (US) from 2019 to 2021. Methods: We conducted a serial cross-sectional analysis of the 2019–2021 National Health Interview Survey by including adults aged ≥ 18 years without reported diagnosed diabetes. We estimated the prevalence of testing for blood glucose within 12 months and the difference in the testing prevalence between 2019 and 2021. Results: The study sample included 82,594 respondents without diabetes in 2019––2021, with a mean age between 46.4 and 46.8 years. Overall, the prevalence of testing for blood glucose decreased significantly from 64.2 % (95 % confidence interval [CI] 63.3 %, 65.1 %) in 2019 to 60.0 % (95 % CI 59.1 %, 60.9 %) in 2021. Among adults who met the United States Preventive Services Task Force's 2015 screening recommendation, the prevalence decreased from 73.4 % (95 % CI 72.2 %, 74.6 %) to 69.5 % (95 % CI 68.3 %, 70.6 %). Although decreases in testing were observed in most groups, the extent of the decline differed by subgroups. Conclusions: Testing for blood glucose decreased in the US during the COVID-19 pandemic. This may have delayed diagnosis and treatment of prediabetes and diabetes, underscoring the importance of continued access to diabetes screening during pandemics. © 2023

INTRODUCTION: This study examined national trends in age, sex, racial and ethnic, and socioeconomic inequalities for diagnosed diabetes prevalence and incidence among US adults from 2008-2021. METHODS: Adults (≥18 years) were from the National Health Interview Survey (2008-2021). The annual between-group variance (BGV) for sex, race, and ethnicity, and the slope index of inequality (SII) for age, education, and poverty-to-income ratio (PIR) along with the average annual percent change (AAPC) were estimated in 2023 to assess trends in inequalities over time in diabetes prevalence and incidence. For BGV and SII, a value of 0 represents no inequality while a value further from 0 represents greater inequality. RESULTS: On average over time, PIR inequalities in diabetes prevalence worsened (SII: -8.24 in 2008 and -9.80 in 2021; AAPC for SII: -1.90%, p=0.003) while inequalities in incidence for age (SII: 17.60 in 2008 and 8.85 in 2021; AAPC for SII: -6.47%, p<0.001), sex (BGV: 0.09 in 2008, 2.05 in 2009, 1.24 in 2010, and 0.27 in 2021; AAPC for BGV: -12.34%, p=0.002), racial and ethnic (BGV: 4.80 in 2008 and 2.17 in 2021; AAPC for BGV: -10.59%, p=0.010), and education (SII: -9.89 in 2008 and -2.20 in 2021; AAPC for SII: 8.27%, p=0.001) groups improved. CONCLUSIONS: From 2008-2021, age, sex, racial and ethnic, and education inequalities in the incidence of diagnosed diabetes improved but persisted. Income-related diabetes prevalence inequalities worsened over time. To close these gaps, future research could focus on identifying factors driving these trends including the contribution of morbidity and mortality.

BACKGROUND: Inflammation may affect long-term kidney function. Diet may play a role in chronic inflammation. We hypothesized that proinflammatory diets increase the risk of progression to kidney failure with replacement therapy (KFRT), and systemic inflammation is a mediator of the effect of diet on progression to KFRT. METHODS: In the 1988-1994 National Health and Nutrition Examination Survey linked to the national ESKD registry, in adults with CKD (eGFR 15-59 ml/min per 1.73 m(2)), aged ≥20 years, we calculated the Adapted Dietary Inflammatory Index (ADII) at baseline from a 24-hour dietary recall and an inflammation score (IS) using average of z scores of four inflammation biomarkers. We explored the association of the ADII and IS with risk of incident KFRT using Cox proportional model, adjusting for sociodemographics, physical activity, Framingham risk score, eGFR, and urinary ACR. We evaluated whether, and to what extent, IS mediated the effect of the ADII on KFRT incidence, using causal mediation analysis. RESULTS: Of 1084 adults with CKD, 109 (10%) developed KFRT. The ADII was associated with increased risk of KFRT (relative hazard [RH] per SD increase (2.56): 1.4 [1.04-1.78]). IS was also associated with KFRT (RH: 1.12; 95% CI, 1.02 to 1.25). Approximately 36% of the association between the ADII and KFRT was explained by IS. CONCLUSIONS: Among adults with CKD, a proinflammatory diet was associated with risk of KFRT, and that association was partially explained by an increase in inflammatory markers. Dietary interventions that reduce inflammation may offer an approach for preventing KFRT.

Background Growing evidence suggests incident cardiovascular disease (CVD) may be a long-term outcome of COVID-19 infection, and chronic diseases, such as diabetes, may influence CVD risk associated with COVID-19. We evaluated the postacute risk of CVD >30 days after a COVID-19 diagnosis by diabetes status. Methods and Results We included adults ≥20 years old with a COVID-19 diagnosis from March 1, 2020 through December 31, 2021 in a retrospective cohort study from the IQVIA PharMetrics Plus insurance claims database. A contemporaneous control group comprised adults without recorded diagnoses for COVID-19 or other acute respiratory infections. Two historical control groups comprised patients with or without an acute respiratory infection. Cardiovascular outcomes included cerebrovascular disorders, dysrhythmia, inflammatory heart disease, ischemic heart disease, thrombotic disorders, other cardiac disorders, major adverse cardiovascular events, and any CVD. The total sample comprised 23 824 095 adults (mean age, 48.4 years [SD, 15.7 years]; 51.9% women; mean follow-up, 8.5 months [SD, 5.8 months]). In multivariable Cox regression models, patients with a COVID-19 diagnosis had a significantly greater risk of all cardiovascular outcomes compared with patients without a diagnosis of COVID-19 (hazard ratio [HR], 1.66 [1.62-1.71], with diabetes; HR, 1.75 [1.73-1.78], without diabetes). Risk was attenuated but still significant for the majority of outcomes when comparing patients with COVID-19 to both historical control groups. Conclusions In patients with COVID-19 infection, postacute risk of incident cardiovascular outcomes is significantly higher than among controls without COVID-19, regardless of diabetes status. Therefore, monitoring for incident CVD may be essential beyond the first 30 days after a COVID-19 diagnosis.

AIMS: Among adults with diabetes in the United States, we evaluated anemia prevalence by CKD status as well as the role of CKD and anemia, as potential risk factors for all-cause mortality. METHODS: In a retrospective cohort study, we included 6,718 adult participants with prevalent diabetes from the 2003-March 2020 National Health and Nutrition Examination Survey (NHANES), a nationally representative sample of the non-institutionalized civilian population in the United States. Cox regression models evaluated the role of anemia and CKD, alone or combined, as predictors of all-cause mortality. RESULTS: Anemia prevalence among adults with diabetes and CKD was 20%. Having anemia or CKD alone, compared with having neither condition, was significantly associated with all-cause mortality (anemia: HR=2.10 [1.49-2.96], CKD: HR=2.24 [1.90-2.64]). Having both conditions conferred a greater potential risk (HR=3.41 [2.75-4.23]). CONCLUSIONS: Approximately one-quarter of the adult US population with diabetes and CKD also has anemia. The presence of anemia, with or without CKD, is associated with a two- to threefold increased risk of death by compared with adults who have neither condition, suggesting that anemia may be a strong predictor of death among adults with diabetes.

INTRODUCTION: Hypertension and diabetes are associated with increased COVID-19 severity, yet less is known about COVID-19 outcomes across levels of disease control for these conditions. METHODS: All adults aged 20 years with COVID-19 between March 1, 2020 and March 15, 2021 in 42 healthcare systems in National Patient-Centered Clinical Research Network were identified. RESULTS: Among 656,049 adults with COVID-19, 41% had hypertension, and 13% had diabetes. Of patients with classifiable hypertension, 35% had blood pressure <130/80 mmHg, 40% had blood pressure of 130139/8089 mmHg, 21% had blood pressure of 140159/9099 mmHg, and 6% had blood pressure 160/100 mmHg. Severe COVID-19 outcomes were more prevalent among those with blood pressure of 160/100 than among those with blood pressure of 130-139/80-89, including hospitalization (23.7% [95% CI=23.0, 24.4] vs 11.7% [95% CI=11.5, 11.9]), receipt of critical care (5.5% [95% CI=5.0, 5.8] vs 2.4% [95% CI=2.3, 2.5]), receipt of mechanical ventilation (3.0% [95% CI=2.7, 3.3] vs 1.2% [95% CI=1.1, 1.3]), and 60-day mortality (4.6% [95% CI=4.2, 4.9] vs 1.8% [95% CI=1.7, 1.9]). Of patients with classifiable diabetes, 44% had HbA1c <7%, 35% had HbA1c 7% to <9%, and 21% had HbA1c 9%. Hospitalization prevalence was 31.3% (95% CI=30.7, 31.9) among those with HbA1c <7% vs 40.2% (95% CI=39.4, 41.1) among those with HbA1c 9%; other outcomes did not differ substantially by HbA1c. CONCLUSIONS: These findings highlight the importance of appropriate management of hypertension and diabetes, including during public health emergencies such as the COVID-19 pandemic.

AIMS: Elevated triglycerides (TG) are associated with development and progression of kidney disease, and TG distributions across lipoprotein subclasses predict kidney dysfunction in adults with type 1 diabetes (T1D). Little is known regarding these relationships in youth. METHODS: In this single center study conducted from October 2018-2019, lipid constituents from lipoprotein subclasses were quantified by targeted nuclear magnetic resonance spectroscopy. Glomerular filtration rate (GFR), renal plasma flow (RPF), afferent arteriolar resistance (R(A)), efferent arteriolar resistance (R(E)), intraglomerular pressure (P(GLO)), urine albumin-to-creatinine ratio (UACR), and chitinase-3-like protein 1 (YKL-40), a marker of kidney tubule injury, were assessed. Cross-sectional relationships were assessed by correlation and multivariable linear regression (adjusted for age, sex, HbA1c) models. RESULTS: Fifty youth with T1D (age 16 ± 3 years, 50 % female, HbA1c 8.7 ± 1.3 %, T1D duration 5.7 ± 2.6 years) were included. Very-low-density lipoprotein (VLDL)-TG concentrations correlated and associated with intraglomerular hemodynamic function markers including GFR, P(GLO), UACR, as did small low-density lipoprotein (LDL)-TG and small high-density lipoprotein (HDL)-TG. YKL-40 correlated with all lipoprotein subclasses. CONCLUSION: TG within lipoprotein subclasses, particularly VLDL, associated with P(GLO,) GFR, albuminuria, and YKL-40. Lipid perturbations may serve as novel targets to mitigate early kidney disease.

AIMS/HYPOTHESIS: Mortality has declined in people with type 1 diabetes in recent decades. We examined how the pattern of decline differs by country, age and sex, and how mortality trends in type 1 diabetes relate to trends in general population mortality. METHODS: We assembled aggregate data on all-cause mortality during the period 2000-2016 in people with type 1 diabetes aged 0-79 years from Australia, Denmark, Latvia, Scotland, Spain (Catalonia) and the USA (Kaiser Permanente Northwest). Data were obtained from administrative sources, health insurance records and registries. All-cause mortality rates in people with type 1 diabetes, and standardised mortality ratios (SMRs) comparing type 1 diabetes with the non-diabetic population, were modelled using Poisson regression, with age and calendar time as quantitative variables, describing the effects using restricted cubic splines with six knots for age and calendar time. Mortality rates were standardised to the age distribution of the aggregate population with type 1 diabetes. RESULTS: All six data sources showed a decline in age- and sex-standardised all-cause mortality rates in people with type 1 diabetes from 2000 to 2016 (or a subset thereof), with annual changes in mortality rates ranging from -2.1% (95% CI -2.8%, -1.3%) to -5.8% (95% CI -6.5%, -5.1%). All-cause mortality was higher for male individuals and for older individuals, but the rate of decline in mortality was generally unaffected by sex or age. SMR was higher in female individuals than male individuals, and appeared to peak at ages 40-70 years. SMR declined over time in Denmark, Scotland and Spain, while remaining stable in the other three data sources. CONCLUSIONS/INTERPRETATION: All-cause mortality in people with type 1 diabetes has declined in recent years in most included populations, but improvements in mortality relative to the non-diabetic population are less consistent.

The incidence and prevalence of youth-onset type 2 diabetes mellitus (T2DM) and its complications are increasing worldwide. Youth-onset T2DM has been reported in all racial and ethnic groups, but Indigenous peoples and people of colour are disproportionately affected. People with youth-onset T2DM often have a more aggressive clinical course than those with adult-onset T2DM or those with type 1 diabetes mellitus. Moreover, the available treatment options for children and adolescents with T2DM are more limited than for adult patients. Intermediate complications of youth-onset T2DM, such as increased albuminuria, often develop in late childhood or early adulthood, and end-stage complications, including kidney failure, develop in mid-life. The increasing frequency, earlier onset and greater severity of childhood obesity in the past 50 years together with increasingly sedentary lifestyles and an increasing frequency of intrauterine exposure to diabetes are important drivers of the epidemic of youth-onset T2DM. The particularly high risk of the disease in historically disadvantaged populations suggests an important contribution of social and environmental factors, including limited access to high-quality health care, healthy food choices and opportunities for physical activity as well as exposure to stressors including systemic racism and environmental pollutants. Understanding the mechanisms that underlie the development and aggressive clinical course of youth-onset T2DM is key to identifying successful prevention and management strategies.

BACKGROUND: Diabetes is a major public health issue. Because lifetime risk, life expectancy, and years of life lost are meaningful metrics for clinical decision making, we aimed to estimate these measures for type 2 diabetes in the high-income setting. METHODS: For this multinational, population-based study, we sourced data from 24 databases for 23 jurisdictions (either whole countries or regions of a country): Australia; Austria; Canada; Denmark; Finland; France; Germany; Hong Kong; Hungary; Israel; Italy; Japan; Latvia; Lithuania; the Netherlands; Norway; Scotland; Singapore; South Korea; Spain; Taiwan; the UK; and the USA. Our main outcomes were lifetime risk of type 2 diabetes, life expectancy in people with and without type 2 diabetes, and years of life lost to type 2 diabetes. We modelled the incidence and mortality of type 2 diabetes in people with and without type 2 diabetes in sex-stratified, age-adjusted, and calendar year-adjusted Poisson models for each jurisdiction. Using incidence and mortality, we constructed life tables for people of both sexes aged 20-100 years for each jurisdiction and at two timepoints 5 years apart in the period 2005-19 where possible. Life expectancy from a given age was computed as the area under the survival curves and lifetime lost was calculated as the difference between the expected lifetime of people with versus without type 2 diabetes at a given age. Lifetime risk was calculated as the proportion of each cohort who developed type 2 diabetes between the ages of 20 years and 100 years. We estimated 95% CIs using parametric bootstrapping. FINDINGS: Across all study cohorts from the 23 jurisdictions (total person-years 1 577 234 194), there were 5 119 585 incident cases of type 2 diabetes, 4 007 064 deaths in those with type 2 diabetes, and 11 854 043 deaths in those without type 2 diabetes. The lifetime risk of type 2 diabetes ranged from 16·3% (95% CI 15·6-17·0) for Scottish women to 59·6% (58·5-60·8) for Singaporean men. Lifetime risk declined with time in 11 of the 15 jurisdictions for which two timepoints were studied. Among people with type 2 diabetes, the highest life expectancies were found for both sexes in Japan in 2017-18, where life expectancy at age 20 years was 59·2 years (95% CI 59·2-59·3) for men and 64·1 years (64·0-64·2) for women. The lowest life expectancy at age 20 years with type 2 diabetes was observed in 2013-14 in Lithuania (43·7 years [42·7-44·6]) for men and in 2010-11 in Latvia (54·2 years [53·4-54·9]) for women. Life expectancy in people with type 2 diabetes increased with time for both sexes in all jurisdictions, except for Spain and Scotland. The life expectancy gap between those with and without type 2 diabetes declined substantially in Latvia from 2010-11 to 2015-16 and in the USA from 2009-10 to 2014-15. Years of life lost to type 2 diabetes ranged from 2·5 years (Latvia; 2015-16) to 12·9 years (Israel Clalit Health Services; 2015-16) for 20-year-old men and from 3·1 years (Finland; 2011-12) to 11·2 years (Israel Clalit Health Services; 2010-11 and 2015-16) for 20-year-old women. With time, the expected number of years of life lost to type 2 diabetes decreased in some jurisdictions and increased in others. The greatest decrease in years of life lost to type 2 diabetes occurred in the USA between 2009-10 and 2014-15 for 20-year-old men (a decrease of 2·7 years). INTERPRETATION: Despite declining lifetime risk and improvements in life expectancy for those with type 2 diabetes in many high-income jurisdictions, the burden of type 2 diabetes remains substantial. Public health strategies might benefit from tailored approaches to continue to improve health outcomes for people with diabetes. FUNDING: US Centers for Disease Control and Prevention and Diabetes Australia.

The prevalence of kidney failure warranting dialysis or transplantation more than doubled between 2000 and 2019 to nearly 800,000 persons in the United States, with diabetes as the leading cause in 47% of those affected.1,2 The incidence of chronic kidney disease (CKD) among patients with diabetes is unknown, yet such data are vital for identifying high-risk populations, determining the effectiveness of interventions, and assessing the effects on health care delivery and public health responses.

AIM: To examine changes in racial and ethnic disparities in glucose-lowering drugs (GLD) use and glycated haemoglobin A1c in US adults with diabetes from 2005 to 2018. METHODS: We conducted pooled cross-sectional analysis using data from the 2005-2018 Medical Expenditure Panel Surveys, and the 2005-2018 National Health and Nutrition Examination Survey. Individuals ≥18 years with diabetes were included. Racial and ethnic disparities were measured in (a) newer non-insulin GLD use; (b) insulin analogue use; (c) non-insulin GLDs adherence; (d) insulin adherence; and (e) glucose management, along with (f) the proportion of the disparities explained by potential contributing factors. RESULTS: From 2005 to 2018, racial and ethnic disparities persisted in newer GLD use, non-insulin GLDs adherence, insulin analogue use and glucose management. In 2018, compared with non-Hispanic white adults, non-Hispanic black, Hispanic and other race/ethnicity groups had lower rates of using newer GLDs (adjusted risk ratio: 0.44, 0.52, 0.64, respectively; p < .05 for all) and insulin analogues (adjusted risk ratio: 0.93, 0.89, 0.95, respectively; p < .05 for all except other groups), lower non-insulin GLD adherence (proportion of days covered: -4.5%, -5.6%, -4.3%, respectively; p < .05 for all), higher glycated haemoglobin A1c (0.29%, 0.32%, 0.02%, respectively; p < .05 for all except other group), and similar insulin adherences. Socioeconomic and health status were the main contributors to these disparities. CONCLUSIONS: Our findings provide evidence of racial and ethnic disparities in newer GLD use and quality of care in glucose management. Our study results can inform decision-makers of the status of racial and ethnic disparities and identify ways to reduce these disparities.

INTRODUCTION: Mortality is an important long-term indicator of the public health impact of chronic kidney disease (CKD). We investigated the role of individual comorbidities and multimorbidity on age-specific mortality risk among US veterans with new-onset CKD. METHODS: The cohort included 892,005 veterans aged 18 years with incident CKD stage 3 between January 2004 and April 2018 in the US Veterans Health Administration (VHA) system and followed until death, December 2018, or up to 10 years. Incident CKD was defined as the first-time estimated glomerular filtration rate (eGFR) was <60 mL/min/1.73 m2 for >3 months. Comorbidities were ascertained using inpatient and outpatient clinical records in the VHA system and Medicare claims. We estimated death rates for any cardiovascular disease (CVD, a composite of 6 CVD conditions) and 15 non-CVD comorbidities, and adjusted risks of death (hazard ratio [HR], 95% confidence interval [CI]) overall and by age group at CKD incidence. RESULTS: At CKD incidence, the mean age was 72 years, and 97% were male; the mean eGFR was 52 mL/min/1.73 m2, and 95% had 2 comorbidities (median, 4) in addition to CKD. During a median follow-up of 4.5 years, among the 16 comorbidities, CVD was associated with the highest relative risk of death in younger veterans (HR 1.96 [95% CI: 1.61-2.37] in ages 18-44 years and HR 1.66 [1.63-1.70] in ages 45-64 years). Dementia was associated with the highest relative risk of death among older veterans (HR 1.71 [1.68-1.74] in ages 65-84 years and HR 1.69 [1.65-1.73] in ages 85-100 years). The additive effect of multimorbidity on risk of death was stronger in younger than older veterans. Compared to having 1 or no comorbidity at CKD onset, the risk of death with 5 comorbidities was >7-fold higher among veterans aged 18-44 years and >2-fold higher among veterans aged 85-100 years. CONCLUSION: The large burden of comorbidities in US veterans with newly identified CKD places them at the risk of premature death. Compared with older veterans, younger veterans with multiple comorbidities, particularly with CVD, at CKD onset are at an even higher relative risk of death.

RATIONALE & OBJECTIVE: The US Military Health System (MHS) is a global health care network with a diverse population that is more representative of the US population than other study cohorts and with fewer disparities in health care access. We aimed to examine the prevalence of chronic kidney disease (CKD) in the MHS and within demographic subpopulations. STUDY DESIGN: Multiple cross-sectional analyses of demographic and claims-based data extracted from the MHS Data Repository, 1 for each fiscal year from 2006-2015. SETTING & POPULATION: Multicenter health care network including active-duty military, retirees, and dependents. The average yearly sample size was 3,285,348 individuals. EXPOSURES: Age, sex, race, active-duty status, and active-duty rank (a surrogate for socioeconomic status). OUTCOME: CKD, defined as the presence of matching International Classification of Diseases, Ninth Revision, codes on either 1 or more inpatient or 2 or more outpatient encounters. ANALYTICAL APPROACH: t test for continuous variables and χ(2) test for categorical variables; multivariable logistic regression for odds ratios. RESULTS: For 2015, the mean (standard deviation) age was 38 (16). Crude CKD prevalence was 2.9%. Age-adjusted prevalence was 4.9% overall-1.9% active-duty and 5.4% non-active-duty individuals. ORs for CKD were calculated with multiple imputations to account for missing data on race. After adjustment, the ORs for CKD (all P < 0.001) were 1.63 (95% CI, 1.62-1.64) for an age greater than 40 years, 1.16 (95% CI, 1.15-1.17) for Black race, 1.15 (95% CI, 1.14-1.16) for senior enlisted rank, 0.94 (95% CI, 0.93-0.95) for women, and 0.50 (95% CI, 0.49-0.51) for active-duty status. LIMITATIONS: Retrospective study based on International Classification of Diseases, Ninth Revision, coding. CONCLUSIONS: Within the MHS, older age, Black race, and senior enlisted rank were associated with a higher risk of CKD, whereas female sex and active-duty status were associated with a lower risk.

BACKGROUND: Both incidence and mortality of diagnosed diabetes have decreased over the past decade. However, the impact of these changes on key metrics of diabetes burden-lifetime risk (LR), years of potential life lost (YPLL), and years spent with diabetes-is unknown. METHODS: We used data from 653,811 adults aged ≥18 years from the National Health Interview Survey, a cross-sectional sample of the civilian non-institutionalized population in the United States. LR, YPLL, and years spent with diabetes were estimated from age 18 to 84 by survey period (1997-1999, 2000-2004, 2005-2009, 2010-2014, 2015-2018). The age-specific incidence of diagnosed diabetes and mortality were estimated using Poisson regression. A multistate difference equation accounting for competing risks was used to model each metric. RESULTS: LR and years spent with diabetes initially increased then decreased over the most recent time periods. LR for adults at age 20 increased from 31.7% (95% CI: 31.2-32.1%) in 1997-1999 to 40.7% (40.2-41.1%) in 2005-2009, then decreased to 32.8% (32.4-33.2%) in 2015-2018. Both LR and years spent with diabetes were markedly higher among adults of non-Hispanic Black, Hispanic, and other races compared to non-Hispanic Whites. YPLL significantly decreased over the study period, with the estimated YPLL due to diabetes for an adult aged 20 decreasing from 8.9 (8.7-9.1) in 1997-1999 to 6.2 (6.1-6.4) in 2015-2018 (p = 0.02). CONCLUSION: In the United States, diabetes burden is declining, but disparities by race/ethnicity remain. LR remains high with approximately one-third of adults estimated to develop diabetes during their lifetime.

This article describes trends in end-stage kidney disease in the US between 2000 and 2019, when a 42% increase in incident cases and a 119% increase in prevalent cases of end-stage kidney disease were observed. Hypertension and diabetes mellitus were the primary causes of both incident and prevalent cases of end-stage kidney disease. These trends suggest there will be an ongoing increase in the demand for organ transplantation, a potential negative impact on future organ supply, and underscore the need for increased access to kidney transplantation nationally.

BACKGROUND: We compared plasma metabolites of amino acid oxidation and the tricarboxylic acid (TCA) cycle in youth with and without type 1 diabetes mellitus (T1DM) and related the metabolites to glomerular filtration rate (GFR), renal plasma flow (RPF), and albuminuria. Metabolites associated with impaired kidney function may warrant future study as potential biomarkers or even future interventions to improve kidney bioenergetics. METHODS: Metabolomic profiling of fasting plasma samples using a targeted panel of 644 metabolites and an untargeted panel of 19,777 metabolites was performed in 50 youth with T1DM ≤ 10 years and 20 controls. GFR and RPF were ascertained by iohexol and p-aminohippurate clearance, and albuminuria calculated as urine albumin to creatinine ratio. Sparse partial least squares discriminant analysis and moderated t tests were used to identify metabolites associated with GFR and RPF. RESULTS: Adolescents with and without T1DM were similar in age (16.1 ± 3.0 vs. 16.1 ± 2.9 years) and BMI (23.4 ± 5.1 vs. 22.7 ± 3.7 kg/m(2)), but those with T1DM had higher GFR (189 ± 40 vs. 136 ± 22 ml/min) and RPF (820 ± 125 vs. 615 ± 65 ml/min). Metabolites of amino acid oxidation and the TCA cycle were significantly lower in adolescents with T1DM vs. controls, and the measured metabolites were able to discriminate diabetes status with an AUC of 0.82 (95% CI: 0.71, 0.93) and error rate of 0.21. Lower glycine (r:-0.33, q = 0.01), histidine (r:-0.45, q < 0.001), methionine (r: -0.29, q = 0.02), phenylalanine (r: -0.29, q = 0.01), serine (r: -0.42, q < 0.001), threonine (r: -0.28, q = 0.02), citrate (r: -0.35, q = 0.003), fumarate (r: -0.24, q = 0.04), and malate (r: -0.29, q = 0.02) correlated with higher GFR. Lower glycine (r: -0.28, q = 0.04), phenylalanine (r:-0.3, q = 0.03), fumarate (r: -0.29, q = 0.04), and malate (r: -0.5, q < 0.001) correlated with higher RPF. Lower histidine (r: -0.28, q = 0.02) was correlated with higher mean ACR. CONCLUSIONS: In conclusion, adolescents with relatively short T1DM duration exhibited lower plasma levels of carboxylic acids that associated with hyperfiltration and hyperperfusion. TRIAL REGISTRATION: ClinicalTrials.gov NCT03618420 and NCT03584217 A higher resolution version of the Graphical abstract is available as Supplementary information.